Long‐term oral exposure to safe dose of bisphenol A in association with high‐fat diet stimulate the prostatic lesions in a rodent model for prostate cancer

Facina, Camila Helena; Campos, Silvana G. P.; Gonçalves, Bianca F.; Góes, Rejane Maira; Vilamaior, Patrícia Simone Leite; Taboga, Sebastião Roberto

doi:10.1002/pros.23458

Cited by 24 publications

(17 citation statements)

References 50 publications

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“…14 These findings are consistent with mounting evidence that prenatal and neonatal exposure in rodents to BSA, even at the current safe dose level (<50 μg/kg/d) accepted by the US Food and Drug Administration and the US Environmental Protection Agency and the European Food Safety Authority, 5 is linked to changes in sexual differentiation, defects in male and female reproductive tracts, meiotic abnormalities in fetal oocytes, complications during pregnancy, and increases in malignancies in adult animals. 15 -17 Adolescence is a key point for gonadal development, endocrine hormone synthesis, and metabolic regulation. Therefore, we selected pubertal male mice as the research model to study the effects on their fertility to exposure at “safe” dose and higher dose of BPA.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Exposure to Bisphenol A on Spermatozoon and the Expression of Tight Junction Protein Occludin in Male Mice

Cao

Wang

et al. 2020

Dose-Response

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Although bisphenol A (BPA) has been associated with impaired spermatogenesis, the mechanisms remain unclear. Tight junction occludin plays important roles in spermatogenesis. The objective of the present study was to explore the effects of BPA exposure in adolescent mice. Male mice were orally treated with low-dose (0.05 mg/kg/d), middle-dose (5.0 mg/kg/d), or high-dose (50 mg/kg/d) BPA in corn oil from postnatal day (PND) 35 to 65. Animals were killed on PND 65 and PND 125. On PND 65, the sperm count, sperm motility, and the expression of occludin showed a dose-related decline. On PND 125, the sperm count, sperm motility, and the expression of occludin were in recovery. However, there remained significant decreases in these parameters in the 50 mg/kg/d group on PND 125 compared with the control. The dose-related effects on the measured parameters and occludin expression suggest an early suppressive or damaging effect on the blood–testis barrier followed by recovery after dosing ceased. At a BPA dose of 50 mg/kg/d, recovery did not occur, suggesting that higher doses of BPA may cause irreversible damage to reproduction in male mice.

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Section: Discussionmentioning

confidence: 99%

The Effect of Exposure to Bisphenol A on Spermatozoon and the Expression of Tight Junction Protein Occludin in Male Mice

Cao

Wang

et al. 2020

Dose-Response

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“…7,8 Several risk factors, including age, genetic factors, androgen dependence, sex hormones, environmental factors, and diet, have been implicated in PCa pathogenesis. 9,10 The activation of oncogenes and the suppression of tumor-suppressing genes also perform major contributions to PCa oncogenesis. 11,12 However, the mechanisms involved in the development and progression of PCa are not well understood.…”

Section: Introductionmentioning

confidence: 99%

<p>MicroRNA-939 Directly Targets <em>HDGF</em> to Inhibit the Aggressiveness of Prostate Cancer via Deactivation of the WNT/β-Catenin Pathway</p>

Song¹,

Zhang²,

Zi³

et al. 2020

OTT

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MicroRNA-939 (miR-939) has crucial roles in several types of human cancer. However, the expression profile and precise functions of miR-939 in prostate cancer (PCa) are still unclear. This study aimed to determine miR-939 expression in PCa and explore its roles in PCa tumorigenesis. Methods: miR-939 expression was determined in PCa tissues and cell lines using reverse transcription-quantitative polymerase chain reaction. Cell Counting Kit-8, colony formation, and flow cytometric assays were used to determine the role of miR-939 in PCa cell proliferation and apoptosis in vitro, whereas a tumor xenograft model was generated to evaluate the effect of miR-939 on tumor growth in vivo. Transwell assays were performed to investigate whether miR-939 affects the migration and invasiveness of PCa cells. Results: miR-939 was found to be downregulated in PCa tissues and cell lines, and this downregulation was significantly correlated with tumor stage and lymphatic metastasis. Patients with PCa exhibiting low miR-939 expression had shorter overall survival than those exhibiting high miR-939 expression. Exogenous miR-939 expression suppressed PCa cell proliferation, colony formation, migration, and invasion in vitro; enhanced apoptosis in vitro; and decreased tumor growth in vivo. Investigation of the underlying molecular mechanisms revealed hepatoma-derived growth factor (HDGF) as a direct target gene of miR-939 in PCa. HDGF was found to be significantly upregulated in PCa tissues, and its expression was inversely correlated with miR-939 expression. HDGF silencing and miR-939 upregulation showed similar effects in PCa. Restored HDGF expression counteracted the tumor-suppressive activity of miR-939 overexpression in PCa cells. Furthermore, ectopic miR-939 expression inhibited the WNT/β-catenin pathway activation in PCa both in vitro and in vivo by downregulating HDGF. Conclusion: miR-939 functions as a tumor suppressor during PCa tumorigenesis by directly targeting HDGF and deactivating the WNT/β-catenin pathway, suggesting the miR-939/ HDGF/WNT/β-catenin pathway as an effective target for PCa therapy.

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“…A histopathological study confirmed that long-term BPA exposure and a high-fat diet induced lesions typical of proliferative and inflammatory processes; additionally, some metabolic changes altered the normal prostatic function (107). The dorsolateral lobe was the most affected, showing a high number of lesions in rats administered with BPA and a diet rich in fatty acids, suggesting an additive effect (107). In general, BPA increased the number of epithelial alterations and inflammatory foci, and adding a hypercaloric diet affected similar signaling pathways (107).…”

Section: Effects Of Edcs On Prostatementioning

confidence: 65%

“…BPA exposure has been associated with obesity and endocrine/metabolic disease (106). A histopathological study confirmed that long-term BPA exposure and a high-fat diet induced lesions typical of proliferative and inflammatory processes; additionally, some metabolic changes altered the normal prostatic function (107). The dorsolateral lobe was the most affected, showing a high number of lesions in rats administered with BPA and a diet rich in fatty acids, suggesting an additive effect (107).…”

Section: Effects Of Edcs On Prostatementioning

confidence: 88%

Breast and prostate glands affected by environmental substances (Review)

Bleak

Calaf

2021

Oncol Rep

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Environmental endocrine disruptor chemicals are substances that can alter the homeostasis of the endocrine system in living organisms. They can be released from several products used in daily activities. Once in the organism, they can disrupt the endocrine function by mimicking or blocking naturally occurring hormones due to their similar chemical structure. This endocrine disruption is the most important cause of the well-known hormone-associate types of cancer. Additionally, it is decisive to determine the susceptibility of each organ to these compounds. Therefore, the present review aimed to summarize the effect of different environmental substances such as bisphenol A, dichlorodiphenyltrichloroethane and polychlorinated biphenyls in both the mammary and the prostate tissues. These organs were chosen due to their association with the hormonal system and their common features in carcinogenic mechanisms. Outcomes derived from the present review may provide evidence that should be considered in future debates regarding the effects of endocrine disruptors on carcinogenesis.

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Long‐term oral exposure to safe dose of bisphenol A in association with high‐fat diet stimulate the prostatic lesions in a rodent model for prostate cancer

Abstract: The results indicated that the methodology used was effective in generating metabolic changes, which directly compromised prostatic homeostasis. Diet and BPA appear to modulate the activation of the AR pathway and thereby optimize tumor establishment in the gerbil prostate.

Cited by 24 publications

References 50 publications

The Effect of Exposure to Bisphenol A on Spermatozoon and the Expression of Tight Junction Protein Occludin in Male Mice

The Effect of Exposure to Bisphenol A on Spermatozoon and the Expression of Tight Junction Protein Occludin in Male Mice

<p>MicroRNA-939 Directly Targets <em>HDGF</em> to Inhibit the Aggressiveness of Prostate Cancer via Deactivation of the WNT/β-Catenin Pathway</p>

Breast and prostate glands affected by environmental substances (Review)

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